Copper(I)-Catalyzed Enantioconvergent Borylation of Racemic Benzyl Chlorides Enabled by Quadrant-by-Quadrant Structure Modification of Chiral Bisphosphine Ligands

Article abstract of DOI:10.1002/anie.201906011

The first copper(I)-catalyzed enantioselective borylation of racemic benzyl chlorides has been realized by a quadrant-by-quadrant structure modulation of QuinoxP*-type bisphosphine ligands. This reaction converts racemic mixtures of secondary benzyl chlorides into the corresponding chiral benzylboronates with high enantioselectivity (up to 92 % ee). The results of mechanistic studies suggest the formation of a benzylic radical intermediate. The results of DFT calculations indicate that the optimal bisphosphine-copper(I) catalyst engages in noncovalent interactions that efficiently recognize the radical intermediate, and leads to high levels of enantioselectivity.

Full text of DOI:10.1002/anie.201906011

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Accepted Article
Title: Copper(I)-Catalyzed Enantioconvergent Borylation of Racemic
Benzyl Chlorides Enabled by Quadrant-by-Quadrant Structure
Modulation of Chiral Bisphosphine Ligands
Authors: Hiroaki Iwamoto, Kohei Endo, Yu Ozawa, Yuta Watanabe,
Koji Kubota, Tsuneo Imamoto, and Hajime Ito
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201906011
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10.1002/anie.201906011
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RESEARCH ARTICLE
Copper(I)-Catalyzed Enantioconvergent Borylation of Racemic
Benzyl Chlorides Enabled by Quadrant-by-Quadrant Structure
Modulation of Chiral Bisphosphine Ligands
Hiroaki Iwamoto,[a] Kohei Endo,[a] Yu Ozawa,[a] Yuta Watanabe,[a] Koji Kubota,[a] Tsuneo Imamoto,[b,c]
and Hajime Ito[a,d]
*
Abstract: The first copper(I)-catalyzed enantioselective borylation of
racemic benzyl chlorides has been realized by a quadrant-by-
quadrant structure modulation of QuinoxP*-type three-hindered-
quadrant bisphosphine ligands. This reaction converts racemic
mixtures of secondary benzyl chlorides into the corresponding chiral
benzylboronates with high enantioselectivity (up to 92% ee). The
results of mechanistic studies suggest the formation of a benzylic
radical intermediate. The results of DFT calculations indicate that the
optimal bisphosphine-copper(I) catalyst engages in non-covalent
interactions that efficiently recognize the radical intermediate, which
leads to high levels of enantioselectivity.
addition, molecular transformations via achiral radical
intermediates with chiral catalysts convergently furnish optically
active products from racemic starting materials.[9] Therefore, it has
been anticipated that the enantioselective borylation of achiral
radical intermediates by chiral copper(I) catalysts should provide
optically active alkylboronates from the corresponding racemic
alkyl chlorides (Scheme 1c).[10–13]
Transition-metal-catalyzed enantioselective reactions involving
radical mechanisms are considered challenging molecular
transformations relative to conventional non-radical reactions. In
typical
transition-metal-mediated
reactions,
the
chiral
environment provided by the chiral catalyst leads to
enantioselective recognition of the substrate through strong
intermolecular interactions, as the metal center firmly binds the
substrate. However, the interaction between chiral catalysts and
neutral radical species is typically weak due to the rather long
distance between them, even in the stereoselectivity-determining
transition state.[9,14] Thus, an effective catalyst-design strategy to
achieve high enantioselectivity in radical-mediated reactions is
highly desirable. We envisioned that design flexibility of the chiral
catalyst would be crucial to find the optimal catalyst able to offer
control over unexpected transition states such as those in radical-
mediated reactions (Scheme 1c).
Introduction
Alkylboronates are highly versatile intermediates for organic
synthesis, as the boryl moieties can be converted into various
functional groups in
a
stereospecific manner.[1,2] Classical
synthetic methods involve transmetalation reactions between
organometallic reagents and boron electrophiles. However, such
protocols often require multiple steps, including the laborious
metalation of alkyl halides, and exhibit low functional-group
compatibility due to the highly reactive organometallic
intermediates. In 2012, Marder, Liu, and co-workers as well as our
group reported the first examples of catalytic borylation reactions
of alkyl electrophiles using copper(I) catalysts.[3] These reactions
provide alkylboronates directly from alkyl electrophiles (Scheme
1a).[4–7] Mechanistic studies on such copper(I)-catalyzed
borylation reactions have led to a plausible catalytic cycle that
involves a radical intermediate. Recently, our group has also
reported a copper(I)-catalyzed borylative radical cyclization by
exploiting the reactivity of such radicals (Scheme 1b).[8] In
The P-chirogenic chiral bisphosphine (S,S)-QuinoxP* has been
recognized as a high-performance chiral ligand for various
[a]
Dr. H. Iwamoto, K. Endo, Y. Ozawa, Y. Watanabe, Dr. K. Kubota,
Prof. Dr. H. Ito
Division of Applied Chemistry, Graduate School of Engineering
Hokkaido University, Sapporo, Hokkaido 060-8628 (Japan)
E-mail: hajito@eng.hokudai.ac.jp
[b]
[c]
[d]
Prof. Dr. T. Imamoto
Organic R&D Department, Nippon Chemical Industrial Co., Ltd.,
Kameido, Koto-Ku, Tokyo, 136-8515 (Japan)
Prof. Dr. T. Imamoto
Department of Chemistry, Graduate School of Science, Chiba
University, Yayoi-cho, Inage-ku, Chiba, 263-8522 (Japan)
Prof. Dr. H. Ito
Institute for Chemical Reaction Design and Discovery (WPI-
ICReDD), Hokkaido University (Japan)
Supporting information for this article is given via a link at the end of
the document
Scheme 1. Copper(I)-catalyzed borylation of alkyl electrophiles.
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10.1002/anie.201906011
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RESEARCH ARTICLE
transition-metal-catalyzed reactions.[15] Our group has developed
a method for the modular synthesis and systematic modification
of such quinoxaline-based bisphosphine ligands (QuinoxP*-type
ligands).[16] This design strategy allows the easy modification of
the alkyl motifs on the phosphorus atoms, thus enabling quadrant-
by-quadrant structure modulations. In this work, we describe the
first copper(I)-catalyzed enantioconvergent borylation of racemic
benzyl chlorides with QuinoxP*-type P-chirogenic bisphosphine
ligands to furnish the corresponding optically active
benzylboronates with high enantioselectivity (up to 92% ee). The
reaction mechanism affording such high enantioselectivity was
investigated experimentally and theoretically.
enantioconvergent borylation of racemic chlorides bearing a 1-
naphtyl moiety 1a (Table 1).[16] We began investigating the impact
of steric congestion in quadrant III on the enantioselectivity. The
ligands were constructed by combination of chiral (CP) and
achiral (AP) phosphine modules. The combination of bulkier chiral
phosphine modules [(S)-CP2 and (S)-CP3] than the module
bearing a tert-butyl group [(S)-CP1] and a di-tert-butyl phosphine
module (AP1) decreased and inversed the enantioselectivity. The
reactions with ligands bearing an adamantyl or a tert-octyl group
in quadrant III, i.e., (S)-Quinox-AdtBu2 and (S)-Quinox-tOct-tBu2,
resulted in low enantioselectivity [(S)-Quinox-tBu3: 73%, 17% ee;
(S)-Quinox-AdtBu2: 73%, –7% ee; (S)-Quinox-tOct-tBu2: 62%, –
3% ee]. In contrast, bulky substituents such as diadamantyl
phosphine (AP2) in quadrants I and IV had a considerable impact
on the enantioselectivity. The reaction with (S)-Quinox-tBuAd2,
which contains AP2 and (S)-CP1, showed higher
enantioselectivity than those with ligands bearing (S)-CP2 and
(S)-CP3 units [(S)-Quinox-tBuAd2: 79%, 86% ee; (S)-Quinox-Ad3:
58%, 76% ee; (S)-Quinox-tOctAd2: 48%, 77% ee]. These
investigations revealed that the lower steric congestion in
quadrant III and the higher steric congestion in quadrants I and IV
enhanced the enantioselectivity.[17]
Results and Discussion
Initially, we carried out a ligand screening involving several
commercially available chiral ligands for the copper(I)-catalyzed
enantioselective borylation of a racemic benzyl chloride bearing a
1-naphtyl group (1a; Table S1). Although the bisphosphine
ligands tested in this preliminary screening were suitable for this
reaction, the yield (up to 56%) and enantioselectivity (up to 57%
ee) of (S)-3a were not satisfactory. During the screening, we
observed that borylation product 3a was the major product when
chiral bisphosphine ligands were used, whereas dimerization
products 4 were detected as the major product when chiral
nitrogen-containing ligands were used (Scheme S1). Then, we
tested the C2-symmetrical P-chirogenic bisphosphine ligand
(S,S)-QuinoxP* in the copper(I)-catalyzed enantioselective
borylation of racemic benzyl chloride 1a (Scheme 2).[15b] The
reaction also showed low reactivity toward the borylation product
(S)-3a and a small amount of the dimerization product 4 [45%
yield, 21% ee for (S)-3a; <10% yield for 4] was obtained. In
contrast, we found that the reaction with three-hindered-quadrant
chiral bisphosphine ligand (S)-Quinox-tBu3 smoothly proceeded
to selectively furnish (S)-3a in high yield, albeit with low
enantioselectivity [73% yield, 17% ee for (S)-3a; <10% yield for
4].[15c]
Table 1. Quadrant-by-quadrant structure modulation of quinoxaline-based P-
chirogenic bisphosphine ligands.[a]
[a] Conditions: [Cu(MeCN)4]BF4 (0.025 mmol), ligand (0.025 mmol), 1a (0.5
mmol), bis(pinacolato)diboron (2, 0.6 mmol), and KOMe (0.6 mmol) in Et2O (2.0
mL). The yield of (S)-3a was determined by a GC analysis of the crude material
using an internal standard. Isolated yields are shown in parenthesis. The
enantioselectivity was determined by HPLC analysis after oxidation of the boryl
group of (S)-3a.
Scheme 2. Enantioconvergent borylation of 1a with quinoxaline-based P-
chirogenic bisphosphine ligands.
To achieve high enantioselectivity, we tested a series of
QuinoxP*-type chiral bisphosphine ligands designed by quadrant-
by-quadrant structure modulation for the copper(I)-catalyzed
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Table 2. Substrate scope for the enatioconvergent borylation reaction.[a]
[a] Conditions: [Cu(MeCN)4]BF4 (0.025 mmol), ligand (0.025 mmol), 1 (0.5 mmol), 2 (0.6 mmol), and KOMe (0.6 mmol) in Et2O (2.0 mL). Isolated yield. The
enantioselectivity was determined by HPLC analysis after oxidation of the boryl group of (S)-3. [b] (S)-Quinox-Ad3 was used instead of (S)-Quinox-tBuAd2. [c]
Isolated yield of the corresponding alcohol after oxidation of the borylation product (S)-3.
Once the best-performing QuinoxP*-type chiral bisphosphine
ligand, (S)-Quinox-tBuAd2, was identified through the
aforementioned quadrant-by-quadrant structural modulation, we
examined the substrate scope for the enantioconvergent
borylation of racemic chlorides (Table 2). 1-Naphtyl substrates
bearing alkyl chains longer than a methyl group exhibited high
enantioselectivity [(S)-3a: R = Et, 70%, 86% ee; (S)-3b: R = Me,
68%, 80% ee; (S)-3c: R = n-Bu, 62%, 84% ee; (S)-3d: R = i-Bu,
52%, 82% ee]. Furthermore, the reaction of the 1-naphtyl
60%, 91% ee; (S)-3m: R = i-Bu, 54%, 90% ee, (S)-3n: R = C2H4Ph,
72%, 91% ee], while the reaction of the substrate with a 2-
benzothiophene moiety (1o) somehow afforded dimerization
products, which resulted in low enantioselectivity and yield [(S)-
3o: 18%, 67% ee]. Although a benzofuran-substituted substrate
showed low enantioselectivity [(S)-3p, 58%, 62% ee], Boc-
protected 3-indole-type substrate 1q afforded (S)-3q with
moderate enantioselectivity (68%, 82% ee). Furthermore, tosyl-
protected indole substrate 1r furnished (S)-3r with higher
enantioselectivity (39%, 84% ee) than that obtained for (S)-3q.
These results indicate that different heteroatoms (S, O, or N) in
the heteroaromatic rings as well as protecting groups on the
substrate bearing
a
benzyl group also showed good
enantioselectivity [(S)-3e: R = CH2Ph, 78%, 84% ee]. Then, 2-
naphtyl substrates were tested in this enantioselective borylation
reaction. The product bearing an ethyl group, (S)-3f, was obtained
in slightly lower enantioselectivity than the corresponding 1-
naphtyl product, (S)-3a [R = Et, 64%, 80% ee]. On the other hand,
the product bearing an i-Bu group, (S)-3g, was obtained with
slightly higher enantioselectivity than the corresponding 1-naphtyl
product, (S)-3d [R = i-Bu, 67%, 84% ee]. The reactions of phenyl-
substituted substrates resulted in moderate enantioselectivity
[(S)-3h: R = Et, 75%, 71% ee; (S)-3i: R = Me, 78%, 67% ee; (S)-
3j: R = i-Bu, 78%, 80% ee]. The borylation of 3-benzothiophene-
type substrates with various alkyl groups proceeded with high
enantioselectivity [(S)-3k: R = Et, 66%, 92% ee; (S)-3l: R = n-Bu,
indole (Boc or tosyl) have
a significant impact on the
enantioselectivity of 3-substituted heteroaromatics such as
benzothiophene (S)-3k, benzofuran (S)-3p, and N-protected
indoles (S)-3q and (S)-3r.
This reaction also allowed the gram-scale synthesis of borylation
product (S)-3k under retention of the yield and selectivity (68%,
92% ee). Furthermore, transformations of the corresponding
borylation product were carried out to demonstrate the synthetic
utility of chiral alkylboronate products (S)-3 (Scheme 3). The
homologation of (S)-3k followed by oxidation of the boryl group
afforded an optically active alcohol bearing a benzothiophene
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RESEARCH ARTICLE
moiety in high yield [(S)-5, 70%, 92% ee]. In turn, cross-coupling
of (S)-3k with 3-fluoropyridine gave a chiral compound bearing
two heteroaromatic rings on the stereogenic carbon atom in
moderate yield, albeit with lower enantiospecificity [(R)-6, 34%,
80% ee].[18]
which suggests that the same intermediate is generated from both
(R)-1i and (S)-1i. Based on the aforementioned mechanistic
experiments, we would like to propose a catalytic cycle for the
enantioselective borylation of racemic benzyl chlorides (Figure
1b). Initially, copper(I)-alkoxide A is formed from the cationic
copper(I) salt, ligand, and KOMe. Borylcopper(I) species B is then
generated by reaction of A and diboron 2. Based on the above
stoichiometric reactions, the neutral species B is not able to
promote the highly selective enantioconvergent borylation.[8,19]
Coordination of the alkoxide base to the copper(I) center affords
the reactive cuprate C. Single electron transfer from C to benzyl
chloride 1a generates an achiral benzyl radical intermediate and
copper(II) species D. Subsequent enantioselective borylation of
this benzyl radical furnishes the optically active organoboron
product (S)-3a under concomitant regeneration of copper(I)-
alkoxide A.
Scheme 3. Synthetic utility of chiral alkylboronate (S)-3k.
Subsequently, we conducted stoichiometric reactions to gain
insight into the reaction mechanism (Figure 1a and Scheme S2).
The reaction using one equivalent of KOMe relative to the
copper(I) salt, chiral ligand, and 2 showed lower reactivity and
enantioselectivity (39%, 50% ee) than those of the optimized
reaction using 1.2 equiv. of the alkoxide. In contrast, the addition
of two equivalents of the alkoxide resulted in high
enantioselectivity similar to that of the optimized reaction (71%,
84% ee). These results suggest that an excess of alkoxide is
important for the generation of the catalytic species that affords
high enantioselectivity (Scheme S3). We also examined the
enantioselectivity of the borylation reactions of optically active
benzyl chlorides [(R)-1i: 47% ee and (S)-1i: 46% ee] and found
that (S)-3i was obtained with almost the same selectivity [from
(R)-1i: 83%, 67% ee; from (S)-1i: 69%, 67% ee; Scheme S4],
Figure 1. Mechanistic studies and proposed catalytic cycle.
Figure 2. Computational study for the step determining the enantioselectivity; all calculations were carried out at the UωB97X-D/def2-TZVPD,def2-
TZVP/IEF-PCM(Et2O)//UωB97X-D/def2-SVPD,def2-SVP/gas phase level of theory.
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hydrogen bonding and C–H/π interactions, as well as the steric
repulsion between the neutral catalyst species and the radical
intermediate lead to high enantioselectivity (up to 92% ee). In the
case of heteroaromatic substrates, the electrophilicity of the
radical species was found to be strongly correlated to the
enantioselectivity, suggesting the importance of electrostatic
interactions. Further improvement of the enantioselectivity based
on mechanistic experiments and theoretical calculations are
currently in progress in our laboratories, and the results will be
reported in due course.
To further investigate the mechanism of the enantioselectivity-
determining step, we performed computational calculations on the
transition states of this borylation (Figure 2).[20] The difference in
activation energy values was consistent with the experimental
results for the borylation of 1i (experiment: 67% ee; calculation:
68% ee; Table 2). The important factors determining the
enantioselectivity were evaluated by structural analysis of the
transition states based on non-covalent interactions (NCIPLOT;
Figure S3).[21] The interaction between the benzylic hydrogen
atom and the oxygen atom of the methoxide coordinated to the
copper center, which resembles hydrogen bonding, is shown as
an “attractive” blue isosurface in both transition states.[22] The
boryl group moves toward the sterically less hindered space in
order to avoid steric repulsion with the bulky alkyl substituents of
the ligand, thus creating a rigid chiral environment for an
enantioselective reaction with the radical species. Furthermore, a
strong C–H/π interaction between the phenyl ring of the substrate
and the methyl groups of the B(pin) was observed, as evident
from the large isosurface in the NCIPLOT analysis of the transition
state TS1 for the major enantiomer (S)-3i. Conversely, in TS2,
which leads to the minor enantiomer (R)-3i, the loose contact
between the phenyl ring and the pinacol moiety of the B(pin) unit
suggests the presence of weak C–H/π interactions. In addition,
the steric interaction between the adamantyl moieties of the ligand
and the aromatic substituent of the substrate distorts the
conformation of the copper(II)-complex, thus destabilizing TS2.
This analysis of the C–H/π interactions is consistent with the
experimental results, where larger aryl groups, which should
exhibit stronger C–H/π interactions with the B(pin) moiety than a
Experimental Section
[Cu(MeCN)4]BF4 (7.9 mg, 0.025 mmol), bis(pinacolato)diboron (2) (152.4
mg, 0.60 mmol), (S)-Quinox-tBuAd2 (13.3 mg, 0.025 mmol) and KOMe
(42.1 mg, 0.60 mmol) were placed in an oven-dried reaction vial. After the
vial was sealed with a screw cap containing a TeflonTM-coated rubber
septum, Dry Et2O (2.0 mL) were added in the vial through the rubber
septum using a syringe. After stirring for 30 min, 1a (0.50 mmol) were
added to the mixture. The reaction mixture was stirred for 48 h at 30 ℃.
After the reaction was completed, the reaction mixture was passed through
a short silica gel column eluting with Et2O (30 mL). The crude material was
purified by flash column chromatography (SiO2, dichloromethane/hexane,
typically 0:100–32:68) to give the corresponding benzylboronate (S)-3a.
Acknowledgements
This work was financially supported by the Institute for Chemical
Reaction Design and Discovery (WPI-ICReDD), which was
established by the World Premier International Research Initiative
(WPI), MEXT, Japan, as well as by JSPS KAKENHI (grant
numbers 17H06370 and 18H03907). H. Iwamoto would like to
thank the JSPS for a scholarship (grant number 16J0141006).
Y.O. was supported by “Program for Leading Graduate Schools”
(Hokkaido University “Ambitious Leaders Program”). A part of
computations was performed using Research Center for
Computational Science, Okazaki, Japan.
simple phenyl group, have
a
positive effect on the
enantioselectivity [1-naphtyl (S)-3a: 86% ee; phenyl (S)-3h: 71%
ee; Table 2]. The adamantyl moieties not only induce repulsive
but also attractive interactions such as London dispersion
between the adamantyl moieties and the methyl group in TS1.[23]
This is also in agreement with the experimental results, which
show that bulky alkyl groups have a positive effect on the
enantioselectivity [Me (S)-3i: 67% ee; i-Bu (S)-3j: 80% ee; Table
2]. The efficient combination of a rigid conformation and attractive
and repulsive interactions in the complex contributes to the
realization of this challenging enantioselective recognition of
achiral radical species despite the long distance between the
substrate radical carbon center and the boron atom compared to
that found in typical transition-metal-mediated reactions (TS1: B–
C = 2.89 Å, Cu–C = 3.30 Å; TS2: B–C = 2.93 Å, Cu–C = 3.22
Å).[24,25]
Keywords: Enantioselective Borylation • Chiral Phosphine
Ligands • Copper(I)-Catalyst • Enantioselective Radical Reaction
• DFT Calculations
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Conclusion
[4]
[5]
In summary, we have developed the first copper(I)-catalyzed
enantioconvergent borylation of racemic benzyl chlorides
employing
a
series of quinoxaline-based P-chirogenic
[6]
bisphosphine ligands based on quadrant-by-quadrant structure
modulation. Computational studies revealed that the
sophisticated integration of attractive interactions, such as
[7]
[8]
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10.1002/anie.201906011
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RESEARCH ARTICLE
[9]
For a review on enantioconvergent reactions of racemic-organic halides,
see: (a) G. C. Fu, ACS Cent. Sci. 2017, 3, 692–700. (b) For examples of
enantioconvergent reactions with nickel(II) catalysts, see: (b) A. H.
Cherney, N. T. Kadunce, S. E. Reisman, J. Am. Chem. Soc. 2013, 135,
7442–7445. (c) J. Schmidt, J. Choi, A. T. Liu, M. Slusarczyk, G. C. Fu,
Science 2016, 354, 1265–1269. For an example of an enantioconvergent
reaction with an iron(II) catalyst, see: (d) M. Jin, L. Adak, M. Nakamura,
J. Am. Chem. Soc. 2015, 137, 7128–7134. For examples of
enantioconvergent reactions with copper(II) catalysts, see: (e) J. B.
Langlois, A. Alexakis, Chem. Commun. 2009, 3868–3870. (f) Q. M. Kainz,
C. D. Matier, A. Bartoszewicz, S. L. Zultanski, J. C. Peters, G. C. Fu,
Science 2016, 351, 681–684.
[24] The B–C distances (2.89–2.93 Å) and Cu(II)–C distances (3.22–3.30 Å)
in the transition states TS1 and TS2 are significantly longer than those
for the borylcupration of alkenes [B–C: 1.85–2.01 Å, Cu(I)–C: 1.99–2.08
Å] in the copper(I)-catalyzed hydroboration of terminal alkenes, which is
not a radical reaction; see: ref. 16.
[25] A clear correlation between the corresponding enantioselectivity and the
electrophilicity of the benzylic radical intermediate was found. The
detailed discussion is provided in the Supporting Information (Figure S6,
S7, Table S2 and S3).
[10] During the course of our study, Fu and co-workers reported pioneering
work on a nickel(II)-catalyzed reaction with moderate enantioselectivity
(<88% ee); see: Z. Wang, S. Bachman, A. S. Dudnik, G. C. Fu, Angew.
Chem. Int. Ed. 2018, 57, 14529–14532; Angew. Chem. 2018, 130,
14737–14740.
[11] H. Ito, S. Kunii, M. Sawamura, Nat. Chem. 2010, 2, 972–976.
[12] B. S. L. Collins, C. M. Wilson, E. L. Myers, V. K. Aggarwal, Angew. Chem.
Int. Ed. 2017, 56, 11700–11733; Angew. Chem. 2017, 129, 11860–
11894.
[13] For a review on copper(I)-catalyzed asymmetric borylations with a
diboron reagent, see: (a) D. Hemming, R. Fritzemeier, S. A. Westcott, W.
L. Santos, P. G. Steel, Chem. Soc. Rev. 2018, 47, 7477–7494. For
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10.1002/anie.201906011
Angewandte Chemie International Edition
RESEARCH ARTICLE
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RESEARCH ARTICLE
Enantioselective borylation of
benzyl radical species: the
copper(I)-chiral phosphine
Dr. H. Iwamoto, K. Endo, Y.
Ozawa, Y. Watanabe, Dr. K.
Kubota, Prof. Dr. T. Imamoto,
Prof. Dr. H. Ito*
ligand catalyst developed by the
elaborate quadrant-by-quadrant
structure modulation of the
ligand enabled an asymmetric
borylation of benzyl chlorides.
The non-covalent interactions
such as C–H/π and C–H/O
interaction were essential for
the enantioselective recognition
of the radical intermediate.
Page No. – Page No.
Copper(I)-Catalyzed
Enantioconvergent Borylation
of Racemic Benzyl Chlorides
Enabled by Quadrant-by-
Quadrant Structure Modulation
of Chiral Bisphosphine Ligands
This article is protected by copyright. All rights reserved.